Active demethylation is another process by which DNA methylation patterns can be diversified and is hypothesized to be important in activity dependent transcriptional responses of neurons. Several studies indicate that demethylation may have a role in neurogenesis102 and neurotransmission,103 and implicate TET1 hydroxylation of methylcytosine in the brain.104 In addition, multiple lines of evidence suggest an involvement of activation induced cytidine deaminase (AID or AICDA) in demethylation. AID bound silent methylated OCT4 and NANOG differentiation factor genes and was required for reprogramming of human induced pluripotent cells.105 AID also contributes to the global demethylation that occurs in mouse primordial germ cells,106 and overexpression of AID in culture results in demethylation of hydroxymethylcytosine.104 Interestingly, AID was first characterized for its role in immunoglobulin class switch DNA recombination where it targets transcription induced R loops.107, 108 R loops are hybrid structures of RNA and DNA in which a nascent RNA molecule with high G content (G skew, found frequently in CGIs) displaces one strand of DNA because of increased affinity.109 R loops have recently been demonstrated to protect active CGI promoters genome wide from de novo DNA methylation.110 Altogether, this suggests that active methylation and demethylation may regulate postnatal neuronal maturation in response to transcriptional changes from early life exposures and experiences.. – zi xiutangs This supported our hypothesis that the higher abuse rates relate to more severe symptoms and to patients referred to academic medical centers. Abuse history also seemed to be associated with patients reporting more IBS symptoms (15). But what was still needed was a well characterized population of GI patients who could be properly identified by interview and then studied prospectively for the outcome effects.Top of pageCLINICAL DATAOur group was fortunate to receive NIH support to evaluate our patients in a more rigorous manner (16,17,18,19,20).
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